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Biomedical subjects

E D Vaughan

Publications and source records attributed to E D Vaughan.

At least 91 records · Page 5Linked to original sources

A clinician friendly computerised head and neck oncology audit: the first year results.

Surgical audit is only as good as the information recorded and data entry is often onerous and the domain of the enthusiastic clinician or research follow. A head and neck oncology audit which incorporates a specific software program has been established in our department. The software interface increases the user friendliness of two conventional database systems, ACCESS and SUPERBASE and structures data input for the clinical situation. The program has been designed for ease of use by every clinician irrespective of their computer competence. The departmental prospective audit has been active since January 1993 and the essential details on new patient presentation, assessment, surgery and outcome for the first year are included in this article.

Aged↗

Chronic unilateral ureteral obstruction is associated with interstitial fibrosis and tubular expression of transforming growth factor-beta.

Chronic unilateral ureteral obstruction (UUO) results in interstitial fibrosis and nephron damage associated with irreversible loss of function. Collagen is increased in UUO, but detailed studies of rat renal extracellular matrix changes in UUO have not been carried out. Acute (3-day) obstruction results in increases in renal macrophages and the fibrogenic cytokine transforming growth factor-beta (TGF-beta), but their involvement in longer-term obstruction and fibrosis has not been studied. In the present experiments, kidneys of rats after UUO of 1, 2, 3, 7, 14, 21, and 28 days' duration were used. Trichrome staining, measurement of interstitial volume, and immunohistochemical studies localizing collagens I, III, and IV; laminin; fibronectin; TGF-beta; and macrophages were carried out. We found increases in the interstitial space in both cortex and medulla that (a) were significant by day 7 after UUO and (b) were accompanied by increased deposition of collagen I and collagen III. Collagen IV, laminin, and fibronectin, normally associated with the basement membrane, were found both in a thickened basement membrane and in the interstitial space. Macrophages, not found in sham-operated kidneys, were found in the interstitial space after UUO. TGF-beta was found in sham cortical tubules, but not in medullary tubules. UUO was associated with little change in cortical TGF-beta, whereas at 14 days, TGF-beta was found in dilated medullary tubules. Immunohistochemical findings were confirmed with measurements of tissue TGF-beta. In summary, UUO is associated with interstitial fibrosis. The increase in extracellular matrix is due both to increases in the interstitial collagens I and III and the basement membrane-associated collagen IV, laminin, and fibronectin. Macrophages are increased after UUO, but do not seem to be associated with the fibrogenic cytokine TGF-beta. Medullary tubular synthesis of TGF-beta may be a contributing factor in the fibrosis associated with UUO.

Animals↗

Creation of a volume lesion in the dog prostate using neodymium:YAG laser coagulation: concepts for clinical treatment.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine the geometrical development of a coagulated zone in the canine prostate during free beam side fire Nd:YAG laser coagulation. STUDY DESIGN/MATERIALS AND METHODS: A series of 10 male dogs underwent endoscopic prostatic Nd:YAG fixed position laser coagulation through a suprapubic cystotomy using a right-angle deflecting delivery catheter (Microvasive, Boston, MA) at times varying from 10 to 120 seconds at 30 watts. In addition, two dogs underwent lasing by pulling the catheter at 1 mm/s in four quadrants. Acute gross and microscopic pathology specimens were prepared and the lesion shape and volume determined. RESULTS: Analysis of the coagulated volume showed that during the initial 15 seconds of lasing, the zone of coagulation approximates a sphere centered on the urothelium opposite the laser fiber. However, as lasing progressed, the lesion changed from a sphere to an expanding ellipse. This changing geometry can be explained by the absorption and scatter characteristics of the laser and the temperature equilibrium that is established within the prostate. CONCLUSION: An understanding of this time-dependent geometrical shift from a sphere to an ellipse allows the surgeon to supplement the fixed protocols for lasing at certain positions for given amounts of time. Specific plans can then be established for tissue at the bladder neck, apex, anterior stroma, floor, and irregular prostatic regrowth.

Absorption↗

Inhibition of bladder tumor cell implantation in cauterized urothelium, without inhibition of healing, by a fibronectin-related peptide (GRGDS).

BACKGROUND: Local recurrence after transurethral resection of bladder tumors (TURB) is common and might be diminished if free tumor cells within the bladder are prevented from reattaching. METHODS: In vitro inhibition of murine bladder tumor cells to an approximation of urothelial matrix with agents that might block attachment to components of the extracellular matrix, and in vivo inhibition of attachment in cautery-injured murine bladder. RESULTS: GRGDS, (0.1-2.5 mg/ml), a fibronectin-related peptide, mannose-6-phosphate, (0.1-20 mg/ml), a carbohydrate, and heparin (1-625 units/ml) all inhibited attachment in vitro in a dose-dependent fashion. YIGSR (0.1-2 mg/ml), a laminin-related peptide, did not. Mannose (10 mg/ml) did not significantly inhibit attachment of tumor cells to cauterized urothelium in vivo, whereas there was a 77% reduction of attachment in bladders irrigated with GRGDS (6.25 mg/ml) (p < 0.05), and the appearance of subsequent tumors in the bladder was inhibited. Finally, GRGDS (6.25 mg/ml) did not inhibit healing of the cautery ulcer. CONCLUSIONS: RGD-containing peptides may be useful as adjuvant therapy to decrease local recurrence after TURB and perhaps in other circumstances in which tumor cells spilled into a wound or body cavity threaten surgical success.

Animals↗

Urologic causes of gynecomastia: approach to diagnosis and management.

A 27-year-old man presented with bilateral painful breast enlargement and recent onset right testicular swelling. After appropriate evaluation, a radical orchiectomy was performed, and a Leydig cell tumor was found. The various urologic etiologies for gynecomastia are presented, as are the potential interventions. A rational approach to the patient with new onset breast swelling is presented.

Adrenal Gland Neoplasms↗

The influence of prostate size on cancer detection.

OBJECTIVES: To determine if cancer detection rates vary with prostate size using a sextant core biopsy pattern. METHODS: We reviewed 1021 transrectal ultrasound (TRUS)-guided sextant pattern prostate biopsies to determine if cancer detection varied based on prostate size. Prostate size was determined using a computer generated elliptical estimation method. Sextant core biopsies were taken, and the patients divided into groups based on estimated size of the prostate and biopsy outcome. Large prostates were those that were estimated by TRUS as 50 cc or more. Prostates were considered small if they were less than 50 cc. Groups were compared based on size and biopsy outcome. RESULTS: Adenocarcinoma was detected in 33% (334 of 1021) of the patients. Large prostates were noted in 34% (346 of 1021), of which 23% (80 of 346) had cancer detected by sextant biopsy. Small prostates were noted in 66% (675 of 1021), of which 38% (254 of 675) had cancer detected. The difference in cancer detection in large and small glands using a sextant pattern was statistically significant (P < 0.01). Patients with positive biopsies had significantly smaller prostate sizes (40 cc +/- 26) when compared with those with negative biopsies (51 cc +/- 33) (P < 0.01). Only 14% (8 of 58) of patients with gland sizes 100 cc or greater had positive sextant biopsies while 49% (118 of 239) with prostates 25 cc or less had cancer detected. Multivariate statistical analysis was used to control for differences in age, prostate-specific antigen (PSA), PSA density, TRUS findings, and digital rectal examination between the large and small prostate groups. The difference in cancer detection persisted (P < 0.05) CONCLUSIONS: Currently no evidence exists to support differing cancer rates based on gland size alone. Our cancer detection rate using a sextant pattern was higher in men with prostates less than 50 cc, and patients diagnosed with cancer had significantly smaller prostates than those with a negative sextant biopsy. Our data suggest that significant sampling error may occur in men with large glands, and more biopsies may be needed under these circumstances. The effects of tumor volume, focality, and specimen size in relation to overall gland size may contribute to these findings.

Adenocarcinoma↗

Correlation of histopathologic findings with clinical and radiologic assessments of cervical lymph-node metastases in oral cancer.

The accuracy of preoperative diagnosis of cervical lymph-node metastasis in oral cancer was assessed by comparing the histopathologic findings in 136 sides of neck dissection with physical examination under anaesthesia (EUA) and computerized tomography (CT) assessments of the metastatic status. The overall accuracy of EUA and CT assessments was 72% and 73%, respectively, and a combination of both methods resulted in sensitivity and specificity rates of 55% and 78%, respectively. Twenty-three of the 51 histologically positive necks had been assessed as negative on both EUA and CT. Six of these contained only micro-metastases, and in another 10, the largest positive node was 1.5 cm or less. Extracapsular spread of metastatic carcinoma was found in 12 of the 23 EUA and CT false-negative dissections. Most of the 21 histologically positive necks which had been correctly assessed as positive on both EUA and CT contained enlarged metastatic nodes, fused nodal masses, extensive extracapsular spread, or more than one of these features. Three of the 85 histologically negative necks had been assessed as positive on both EUA and CT; eight had been positive on EUA alone, and another eight on CT alone. Reactive nodal hyperplasia or sialadenitis was seen in most false-positive dissections. We conclude that the accuracy of preoperative diagnosis of metastasis by routine methods remains poor, and that EUA and CT are reliable only in patients with bulky metastatic deposits.

Adolescent↗

Microsatellite instability in squamous cell carcinoma of the head and neck.

Genomic instability or microsatellite instability (MI) in simple repeated sequences was initially recognised in colonic carcinomas and subsequently in other tumours. MI has been associated with mutations in genes concerned with replication and DNA repair. We investigated 34 microsatellite markers in squamous cell carcinoma of the head and neck (SCCHN). Fifty-six tumours, were studied, of which 25 were investigated with ten or more microsatellite markers. In this study we consider two or more microsatellite alterations in a tumour to be diagnostic of MI. We demonstrated that 7/25 (28%) of the tumours had MI at two or more loci and three of these tumours exhibited evidence of 20 or more loci with MI. No correlations were found between MI and previous treatment, site, histological differentiation, positive nodes at pathology, a history of alcohol intake or survival. MI has been demonstrated in T1N0 stage tumours, indicating that these changes may occur early in the disease process. A negative correlation was found between MI and a history of smoking (P = 0.02). Two or more markers of MI were found in three of four non-smokers compared with one of 13 in the smoking group of patients, which suggests a novel mechanism of carcinogenesis in non-smokers.

Carcinoma, Squamous Cell↗

Mutations, expression and genomic instability of the H-ras proto-oncogene in squamous cell carcinomas of the head and neck.

Mutation and overexpression are the main activating mechanisms for the ras family of genes in human cancer and the variable tandem repeat (VTR) located at the 3' end of H-ras has been associated with this risk. In the present study, we have analysed the relative levels of expression of H-ras mRNA in 26 samples of squamous cell carcinomas of the head and neck (SCCHN) by competitive reverse transcription-polymerase chain reaction (competitive RT-PCR) and also investigated whether there is an association between ras expression and alterations in the 3'-VTR region. In addition, we have studied the incidence of point mutations in codon 12 of H-ras, codons 12 and 13 of K-ras and codon 61 of N-ras in 120 SCCHN samples. Our results indicate that only two samples carry mutations, both of which are located in codon 12 of K-ras, but that overexpression of the H-ras proto-oncogene is a frequent event in SCCHN [54% (14/26)] and is associated with a favourable prognosis: 3 of 14 patients with H-ras overexpression have died, whereas 9 of 12 patients with low levels of H-ras expression have died. We have also undertaken an analysis of these results together with our previous investigations on microsatellite instability and loss of heterozygosity in SCCHN, but no associations were found. We therefore conclude that ras mutations are an infrequent event in the progression of the SCCHN in the Western world, whereas overexpression of the H-ras proto-oncogene is a common event.

Base Sequence↗

Accuracy of computerized tomography in the diagnosis of colovesical fistula secondary to diverticular disease.

We reviewed 9 consecutive patients with colovesical fistula secondary to diverticulitis during a 2-year period. Preoperative evaluation included computerized tomography (CT) and a barium enema or colonoscopy in all patients (8 underwent cystoscopy). All patients subsequently underwent laparotomy with a single or multiple staged repair. Using CT criteria for diagnosis of colovesical fistulas, the study accurately predicted the presence and location of fistula in 8 patients, and was suspicious in 1. Findings at cystoscopy only diagnosed 3 fistulas and were suspicious in 4. The remaining diagnostic tests, including excretory urography, barium enema, abdominal plain films, colonoscopy and cystogram, were unremarkable except for a single cystogram and barium enema. In addition to documenting the fistula, CT provided important intraluminal and extraluminal pathological findings helpful in planning subsequent surgery. Thus, CT should be included in the initial evaluation of patients with suspected colovesical fistula.

Aged↗

Survival, metastasis and recurrence of oral cancer in relation to pathological features.

The outcome of 123 patients with squamous cell carcinoma of the oral/oropharyngeal mucosa treated by primary radical surgery and simultaneous neck dissection and followed up for a maximum of 5 years is reported and related to the pathological features of the tumour. Actuarial survival analysis showed the overall 1-year survival probability was 84%, falling to 69% at 2 years, and 65% at 5 years. For patients without lymph node metastasis, the corresponding survival probabilities were 95%, 86% and 86%, respectively; and for patients with metastasis, 71%, 52% and 44%, respectively. In all, 30 patients (24%) died of their oral cancer; 16 (13%) of local recurrence, 10 (8%) of regional recurrence and 4 (3%) of systemic metastases. In addition to lymph node metastasis, survival was related to the site and stage of the primary tumour, histological pattern of invasion, status of the resection margins and, for patients with metastasis, the number and anatomical level of positive nodes and the presence and extent of extracapsular spread. These pathological features are important indicators of tumour behaviour and should be incorporated into protocols for assessment of prognosis.

Adolescent↗

Biopsy of lesions of the male genitourinary tract.

Biopsy of benign and malignant lesions of the male genitourinary tract using a variety of open and endourologic techniques is possible. A multidisciplinary approach involving close communication between clinicians, radiologists, and pathologists is imperative to a favorable outcome. Urologic practice has pioneered many of these techniques, which continue to evolve as new technologies become available.

Adrenal Gland Neoplasms↗

Volume expansion enhances the recovery of renal function and prolongs the diuresis and natriuresis after release of bilateral ureteral obstruction: a possible role for atrial natriuretic peptide.

Plasma atrial natriuretic peptide (ANP) levels are elevated in patients with bilateral ureteral obstruction (BUO). To further evaluate the role of ANP in postobstructive diuresis, natriuresis and recovery of renal function, 3 groups of dogs were studied: Group 1, 6 dogs that underwent 48 hours of unilateral ureteral obstruction (UUO); Group 2, 6 dogs that underwent 48 hours of BUO; and Group 3, 6 dogs volume replete with normal saline during 48 hours of BUO. All 3 groups underwent hourly hemodynamic and clearance studies for 15 hours after the release of obstruction. Group 1 experienced no increase in either urine output or sodium excretion from the ipsilateral or contralateral kidney after release of obstruction. Groups 2 and 3 both experienced an initial diuresis and natriuresis after BUO (p < 0.01). However, in Group 2 diuresis and natriuresis after BUO ceased at 5 and 2 hours, respectively, while in Group 3 both persisted for 10 and 9 hours, respectively. Before obstruction the GFR was similar in all three groups. In Group 1 the GFR decreased significantly in the ipsilateral kidney (34.5 +/- 1.4 to 14.48 +/- 1.5 ml. per minute, (p < 0.01)) and increased significantly in the contralateral kidney (32.4 +/- 2.8 to 44.4 +/- 2.0 ml. per minute, (p < 0.05)) and remained so throughout the postobstruction period. The GFR in Groups 2 and 3 decreased to a similar level 1 hour after release (13.3 +/- 1.7 and 17.5 +/- 3.4 ml. per minute, respectively); however, Group 2 remained decreased during the period after release while group 3 increased to 23.4 +/- 3.4 ml. per minute (p < 0.01) at 11 hours after release of obstruction. In Group 2 the control plasma ANP level was 17.9 +/- 3.7 pg./ml. and was not altered by BUO, whereas ANP increased significantly after 48 hour BUO in Group 3, from 30.6 +/- 6.7 to 63.7 +/- 11.7 pg./ml. (p < 0.01). Before and after 48 hours of BUO, the pulmonary capillary wedge pressure was 5.0 +/- 2.0 mm. Hg and 7.0 +/- 1.0 mm. Hg (NS) in Group 2, while it increased from 7.18 +/- 1.5 mm. Hg to 11.6 +/- 1.9 mm. Hg (p < 0.01) in Group 3. We conclude that volume expansion during BUO enhances postobstructive diuresis and natriuresis and allows a greater recovery of GFR after release of the obstruction. This effect may be mediated through elevated plasma levels of ANP as measured in this study.

Animals↗

Diagnosis and treatment of primary hyperaldosteronism.

OBJECTIVE: To characterize the clinical and laboratory features of primary aldosteronism and to evaluate which diagnostic tests can discriminate surgically curable forms of this syndrome. DESIGN: Retrospective analysis of the following data from 82 patients with primary aldosteronism: blood pressure, serum electrolytes, urinary aldosterone and electrolytes, computed tomographic scans, plasma renin and aldosterone before and during upright posture, atrial natriuretic peptide, and adrenal vein aldosterone and cortisol. Clinical outcomes assessed after treatment included blood pressure, serum electrolytes, and plasma renin activity. RESULTS: Drug therapy was discontinued before diagnostic tests were done in 56 of 82 patients (34 with adenomas and 22 with hyperplasia). Compared with patients with hyperplasia, those with adenomas had higher systolic (184 mm Hg and 161 mm Hg, respectively; P < 0.001) and diastolic blood pressures (112 mm Hg and 105 mm Hg; P = 0.03), lower serum potassium levels (3.0 mmol/L and 3.5 mmol/L; P < 0.001), and higher serum CO2 (P = 0.001), atrial natriuretic peptide (P = 0.008), and urinary 18-methyl oxygenated cortisol metabolite levels (P = 0.02). In patients with adenomas, aldosterone secretion lateralized to one adrenal gland and did not increase during the postural stimulation test; preoperative urinary aldosterone levels were correlated with diastolic pressures (r = 0.58; P = 0.001). Hypertension was "cured" postoperatively in approximately 35% of patients with adenomas and those with hyperplasia (P > 0.2) but was "improved" more frequently in those with adenomas (P = 0.002). Cured patients from both groups were younger than those not cured (mean ages, 43 years and 54 years, respectively; P = 0.002) and had lower preoperative mean plasma renin activity (0.17 ng/mL per hour and 0.50 ng/mL per hour; P < 0.001). All patients with adenomas in whom aldosterone secretion lateralized were either cured or improved. CONCLUSION: Of the 51 patients with primary aldosteronism who had adrenalectomy (43 patients with adenomas and 8 with hyperplasia), those most likely to be cured were younger and had lower plasma renin activity. In patients with adenomas who were cured or improved, aldosterone secretion was more likely to lateralize. Tests that distinguished adenomas from adrenal hyperplasia included the postural stimulation test, urinary excretion rates of 18-oxocortisol and 18-hydroxycortisol, and adrenal vein sampling.

Adenoma↗

The management of the mandible in mouth cancer.

Surgical necessity or the ravages of disease frequently result in the loss of mandibular continuity with consequent disruption of function and form. The role of the maxillofacial surgeon is central to the restoration as far as possible of maximum cosmesis and oral function. The suggestion in the recent consultative document on future organisation of cancer services lends weight to this role where it states 'In future the surgical management of cancer should be carried out by surgeons who specialise in a particular anatomical area'.

Humans↗